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心力衰竭发生过程中免疫细胞浸润的时间框架:来自动物模型的经验教训。

Temporal Frame of Immune Cell Infiltration during Heart Failure Establishment: Lessons from Animal Models.

机构信息

Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Cátedra de Cardiología y Medicina Vascular, Monterrey, Nuevo León 64849, Mexico.

Tecnologico de Monterrey, Hospital Zambrano Hellion, TecSalud, Centro de Investigación Biomédica, San Pedro Garza García, Nuevo León 66278, Mexico.

出版信息

Int J Mol Sci. 2018 Nov 22;19(12):3719. doi: 10.3390/ijms19123719.

Abstract

Heart failure (HF) is a cardiovascular syndrome characterized by maladaptive changes with an underlying inflammatory mediated pathogenesis. Nevertheless, current therapy is aimed at the heart workload and neurohormonal axis; thus, prognosis remains poor. To continue improving treatment, we rely on murine models for a better understanding of HF pathophysiology. Among them, pressure overload HF (PO-HF) animal models are a common strategy. Development of PO-HF is characterized by monocyte infiltration, which orchestrates a cascade of events leading to sustained inflammation and maladaptive changes. Here, we divide the PO-HF model progression into four phases and describe the inflammatory, structural, and gene expression profiles. This division is relevant due to its similarities with clinical hypertensive heart disease progression to HF. Evidence shows improvement in hemodynamic and other local parameters by altering the inflammatory response in a specific immune response at a specific point of time. Thus, it is relevant to focus on the time-dependent immune response interaction in order to provide more effective therapy. This review summarizes the pathogenesis of PO-HF murine models, highlighting the inflammatory events in a time frame view. By this approach, we expect to provide researchers with a better understanding of the intertwining time-dependent events that occur in PO-HF.

摘要

心力衰竭(HF)是一种心血管综合征,其特征为适应性变化,其潜在发病机制为炎症介导。然而,目前的治疗方法旨在减轻心脏负荷和神经激素轴的负担;因此,预后仍然不佳。为了继续改善治疗效果,我们依赖于小鼠模型来更好地了解 HF 的病理生理学。在这些模型中,压力超负荷性 HF(PO-HF)动物模型是一种常见的策略。PO-HF 的发展以单核细胞浸润为特征,这种浸润会引发一系列事件,导致持续的炎症和适应性变化。在这里,我们将 PO-HF 模型的进展分为四个阶段,并描述了炎症、结构和基因表达特征。这种划分是相关的,因为它与临床高血压性心脏病进展为 HF 的过程相似。有证据表明,通过在特定时间点改变特定免疫反应中的炎症反应,可以改善血流动力学和其他局部参数。因此,关注时间依赖性免疫反应的相互作用以提供更有效的治疗方法是很重要的。本综述总结了 PO-HF 小鼠模型的发病机制,强调了在时间范围内的炎症事件。通过这种方法,我们期望为研究人员提供对 PO-HF 中发生的时间依赖性事件的更好理解。

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